A comprehensive pediatric cardio-oncology program: a single institution approach to cardiovascular care for pediatric patients with cancer and childhood cancer survivors.

Cardiovascular complications related to cancer therapies are broad and variable in onset. These complications are the leading cause of non-cancer related morbidity and mortality in childhood cancer survivors and can also impact ongoing cancer treatment. Despite this understanding, dedicated cardio-oncology programs are lacking in pediatric cardiology. In an attempt to respond to these concerns, a risk-stratified, comprehensive cardio-oncology program was established to address the cardiovascular needs including prevention, early diagnosis, and management of patients with and at risk for cardiovascular complications of cancer therapy. This manuscript describes a single institution's experience of building and managing a multidisciplinary pediatric cardio-oncology program with close collaboration among cardiologists, oncologists, advanced cardiology and oncology practice providers, and allied health providers such as a dietitian and psychologist to provide comprehensive cardiovascular care for childhood cancer patients and survivors. In developing this program, emphasis was on the childhood cancer survivor population, as various cardiovascular complications can present many years after cancer treatment.

Cardio-oncology for Pediatric and Adolescent/Young Adult Patients.

OPINION STATEMENT: As chemotherapy continues to improve the lives of patients with cancer, understanding the effects of these drugs on other organ systems, and the cardiovascular system in particular, has become increasingly important. The effects of chemotherapy on the cardiovascular system are a major determinant of morbidity and mortality in these survivors. Although echocardiography continues to be the most widely used modality for assessing cardiotoxicity, newer imaging modalities and biomarker concentrations may detect subclinical cardiotoxicity earlier. Dexrazoxane continues to be the most effective therapy for preventing anthracycline-induced cardiomyopathy. Neurohormonal modulating drugs have not prevented cardiotoxicity, so their widespread, long-term use for all patients is currently not recommended. Advanced cardiac therapies, including heart transplant, have been successful in cancer survivors with end-stage HF and should be considered for these patients. Research on new targets, especially genetic associations, may produce treatments that help reduce cardiovascular morbidity and mortality.

Clinical profile and outcome of glycogen storage disease in Indian children.

We aimed to determine the clinical profile and outcome of Indian children with glycogen storage disorders. Ours was a retrospective study from 2005 to 2018 in 36 children diagnosed on the basis of a liver biopsy. Most (77.7%) presented with abdominal swelling but a quarter with convulsion, four of whom had documented hypoglycaemia associated, doll-like facies or developmental delay. Diarrhoea was found in four patients, ascites in two and portal hypertension in one. One child died, and over half were unfortunately lost to follow-up, though the rest had recurrent seizures, three more developed neutropenia, two recurrent infections, one portal hypertension with epistaxis, one nephrocalcinosis and liver adenoma. Liver function improved in six (37.5%) with normalisation of triglycerides, and four of serum transaminases.

Prevalence and clinical profile of glycogen storage diseases in children from Western India.

AIM OF THE STUDY: To determine the prevalence and clinical profile of glycogen storage diseases (GSD) in children in western India. MATERIAL AND METHODS: This retrospective analysis was conducted over a period of 7 years from 2006 to 2012. All children diagnosed with GSD on liver biopsy were included in the study. Their clinical history, examination, biochemical profile and outcome were noted. RESULTS: Of 751 children, 18 (2.4%) were clinically diagnosed with GSD. Mean age at presentation was 2.3 ±1.3 years. Male : female ratio was 1 : 1. The main presenting features were abdominal distension in 15 (83.3%) patients, hepatomegaly in all 18 (100%), splenomegaly in 11 (61.1%) and jaundice in 2 (11.1%) patients. Four (22.2%) patients had delayed development. Four (22.2%) patients were siblings to an older affected child. Only 1 (5.6%) patient had portal hypertension and 2 (11.1%) had ascites. Only 1 (5.6%) patient had elevated bilirubin levels, 17 (94.4%) had elevated serum glutamic-oxaloacetic transaminase (SGOT) and all 18 (100%) patients had elevated serum glutamic-pyruvic transaminase (SGPT) levels. Nine (69.3%) patients of the 13 tested had acidosis, 1 (9.1%) had elevated uric acid, 2 (11.1%) had neutropenia, 8 (44.4%) experienced hypoglycemia, 4 (22.2%) patients had nephromegaly and only 1 patient showed evidence of cirrhosis in the liver biopsy. Fifteen (83.3%) patients were short. Three out of 6 patients tested had hypertriglyceridemia (50%). One (5.6%) patient died, 9 (50%) patients were lost to followup and the remaining 8 (44.4%) patients continued regular follow-up. CONCLUSIONS: Metabolic acidosis, hypertriglyceridemia, short stature, and hypoglycemia are major problems in children with GSD. Most of the patients are referred late at the time of presentation.

Infantile-onset pompe disease: a tale of two cases.

Pompe disease is a type-II glycogen storage disease, and clinical manifestations include hypertrophic cardiomyopathy and generalised muscular hypotonia. Enzyme replacement therapy has proven to be effective in reversing the ventricular hypertrophy. The outcomes are variable depending on time to diagnosis and severity of the cardiac disease. We describe two contrasting cases of patients with infantile-onset Pompe disease. The first child was diagnosed late and had severe cardiac hypertrophy with respiratory decompensation and ventilator dependence and eventual death. The second case was diagnosed at birth with early initiation of therapy resulting in a good outcome. Our cases highlight the importance of early initiation of enzyme replacement therapy to improve clinical outcomes.

Fulminant hepatitis E in an infant.

Hepatitis E virus (HEV) is an enterically transmitted infection that is typically self-limited. It spreads by fecally contaminated water within endemic areas. Hepatitis E infection occurs in both sporadic and epidemic forms in developing countries. HEV infection is usually subclinical in children but in a pregnant woman, it manifests commonly as fulminant hepatic failure. A few cases of acute liver failure caused primarily by HEV infection in children have been reported. We present a case of fulminant hepatitis E in a 1-year-old child. She showed positive signs of hepatic encephalopathy, jaundice, and coagulopathy and was given symptomatic treatment for the same. She recovered due to the self-limiting nature of HEV infection and prompt symptomatic relief.

Evaluation of CYP2C19, P2Y12, and ABCB1 polymorphisms and phenotypic response to clopidogrel in healthy Indian adults.

INTRODUCTION: CYP2C19 and P2Y12 polymorphisms have been claimed to alter the pharmacodynamic response to clopidogrel. ABCB1 polymorphism has been associated with the efflux of clopidogrel resulting in decreased bioavailability. Due to paucity of data from Indian population, the present study was undertaken to evaluate the association of genetic polymorphisms of CYP2C19, P2Y12, and ABCB1 with inhibition of platelet aggregation (IPA) by clopidogrel. METHODS: Healthy adults (n = 90) of either gender were administered single dose of 300 mg clopidogrel. Baseline, 4 h postdose, and day 7 assessment of platelet aggregation and genotype of CYP2C19, P2Y12, and ABCB1 were carried out using standardized laboratory methods. The difference in the maximum platelet aggregation (MPA) between baseline and 4 h postdose was considered as delta-MPA (DMPA), and percentage change of MPA at 4 h from baseline was considered as IPA. Those with an IPA of <30% were considered as poor responders. Inferential statistics was applied to find out significant difference of these parameters between various groups of genetic polymorphisms. RESULTS: Mean (standard deviation [SD]) of MPA (%) at baseline, 4 h postdose, and day 7 were 78 (5), 56 (16), and 71 (8), respectively. Similarly, mean (SD) of DMPA (%) and IPA (%) were 23 (17) and 29 (21), respectively. A total of 54/90 (60%) cases were found to be poor responders to clopidogrel. A wild genotype (*1/*1) of CYP2C19 was observed in 35 (40.2%), 42 (48.3%) had *1/*2, 2 (2.3%) individuals had *1/*3, and 8 (9.2%) had *2/*2 mutant genotypes. Although statistically not significant (P = 0.09), a trend was observed in having decreased inhibition values (both MPA and IPA) as we proceed from wild genotype (*1/*1) to mutant genotypes in the order of *1/*2, *1/*3, and *2/*2. Similarly, in P2Y12, a wild haplotype (H1/H1) was present in 77 (89.5%) and 9 (10.5%) individuals had H1/H2 type. A statistically significant difference in DMPA and IPA was observed with more IPA by clopidogrel in individuals with H2 haplotype. No association was observed between the carriers and noncarriers of mutant (T) allele of ABCB1. CONCLUSION: A trend of decrease in the IPA with CYP2C19 genotypes and an increase in the same with the H2 haplotype of P2Y12 following clopidogrel in Indian healthy adults were observed. Assessment of genetic polymorphisms of the same may aid in personalizing the therapy with clopidogrel.